The vomeronasal or accessory olfactory system (AOS) detects and processes pheromone signaling information from the environment. In mice, pheromonal communication is involved in establishing dominance hierarchies in males, and plays roles in promoting, synchronizing, and maintaining fertility in females. The AOS remains poorly understood compared to other communicative sensory modalities, including olfaction through the main olfactory system. Despite key differences in the neural circuitry, most of our current thinking about the AOS derives from results obtained in the main olfactory system. This research plan is designed to increase our understanding of the first central brain structure in the AOS, the accessory olfactory bulb (AOB). This application focuses on the inhibitory granule cells (GCs), which modulate the principal mitral cells of the AOB through GABAergic dendro-dendritic synapses. There are no current published reports on GC tuning to natural pheromone stimulation, despite evidence for their involvement in lateral inhibition and learning. The first Specific Aim of this application is to determine whether sensory tuning of AOB GCs is broader or sharper than tuning of vomeronasal sensory neurons (VSNs). We will determine tuning by recording action potential responses in each cell type while stimulating with sulfated steroid compounds our lab has shown to activate VSNs. We will make single extracellular electrode recordings from GCs and multi-electrode array recordings from VSNs in acute, ex vivo preparations. The second Specific Aim investigates potential links between GC morphology and physiological function. The specific connectivity patterns between mitral cells and GCs in the AOB are likely to underlie the tuning properties of each cell. We will acquire 3-dimensional morphological information from physiologically- characterized AOB GCs after labeling each recorded cell with a cytoplasmic dye. We will quantify the position, span, and density of the cell processes using fluorescence microscopy. We will use these data to determine whether structural properties correlate with specific tuning qualities of the cells. The proposed studies will fill a substantial gap in our understanding of pheromone communication in vertebrates. Relevance: Mammalian behavior is informed strongly by pheromonal communication, but little is known about how neurons in the pheromone-associated areas of the brain process social cues. This research plan investigates the responsiveness of inhibitory granule neurons in pheromone-associated brain areas in mice in order to fill a substantial gap in our understanding of this sensory pathway.